Description:
The purpose of study is to compare bladder intact-event free survival (BI-EFS) in
participants receiving TAR-200 in combination with cetrelimab versus concurrent
chemoradiotherapy.
Title
- Brief Title: A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
- Official Title: A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder Who Are Not Receiving Radical Cystectomy
Clinical Trial IDs
- ORG STUDY ID:
CR108917
- SECONDARY ID:
2020-002620-36
- SECONDARY ID:
17000139BLC3001
- NCT ID:
NCT04658862
Conditions
- Urinary Bladder Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
Cetrelimab | JNJ-63723283 | TAR-200 + Cetrelimab |
TAR-200 | JNJ-17000139 | TAR-200 + Cetrelimab |
Cisplatin | | Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy |
Gemcitabine | | Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy |
Purpose
The purpose of study is to compare bladder intact-event free survival (BI-EFS) in
participants receiving TAR-200 in combination with cetrelimab versus concurrent
chemoradiotherapy.
Detailed Description
The TAR-200 is an investigational drug delivery system. Cetrelimab (JNJ-63723283) is a fully
human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed cell
death protein 1 (PD-1). Study consists of screening phase of 42 days, treatment phase and
follow up phase. The total duration of study will be up to 8 years. Efficacy evaluation
includes disease assessment (Cystoscopy/TURBT Biopsy/Pathology) and Patient Reported Outcomes
(Quality of Life Assessments) and safety assessments includes vital sign measurements,
12-lead electrocardiogram (ECG), physical examinations, clinical laboratory tests,
cystoscopic examination, anti-drug antibody (ADA) assessments, concomitant
treatments/procedures and adverse event monitoring.
Trial Arms
Name | Type | Description | Interventions |
---|
TAR-200 + Cetrelimab | Experimental | Participants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with Cetrelimab. | |
Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy | Active Comparator | Participants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 6 treatment weeks or gemcitabine intravenously twice weekly for 6 treatment weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray [Gy], bladder only) for up to 6.5 treatment weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks. | |
Eligibility Criteria
Inclusion Criteria:
- Ineligible for or have elected not to undergo radical cystectomy
- All adverse events associated with any prior surgery and/or intravesical therapy must
have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Grade less than (<) 2 prior to randomization
- Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
- Thyroid function tests within normal range or stable on hormone supplementation per
investigator assessment.
- Adequate bone marrow, liver, and renal function: Bone marrow function (without the
support of cytokines or erythropoiesis-stimulating agent in preceding two weeks):
Absolute neutrophil count (ANC) greater than or equal to (>=) 1,500/cubic millimeters
(mm^3); Platelet count >=80,000/mm^3; Hemoglobin >=9.0 grams per deciliter (g/dL);
Liver function: (Total bilirubin less than or equal to (<=) 1.5 * upper limit of
normal (ULN) or direct bilirubin <= ULN for participants with total bilirubin levels
greater than (>)1.5*ULN (except participants with Gilbert's Syndrome, who must have a
total bilirubin < 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) less than or equal to (<=) 2.5* institutional ULN); Renal
function: Creatinine clearance >40 mL/min using the Cockcroft-Gault formula
Exclusion Criteria:
- Must not have had urothelial carcinoma or histological variant at any site outside of
the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract
(including renal pelvis and ureter) is allowable if treated with complete
nephrouretrectomy more than 24 months prior to initiating study
- Must not have diffuse CIS based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS
is defined as the presence of at least 4 distinct CIS lesions in the bladder at the
time of the Screening re-TURBT
- Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local
radiology staging (chest, abdomen, and pelvis must be performed using Computed
tomography [CT] or Magnetic resonance imaging [MRI]) within 42 days prior to
randomization
- Presence of any bladder or urethral anatomic feature that, in the opinion of the
investigator, may prevent the safe placement, indwelling use, or removal of TAR 200
- Evidence of bladder perforation during diagnostic cystoscopy
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Time from Randomization to the First Bladder Intact Event-free Survival (BI-EFS) event |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | Time from randomization to the first BI-EFS event includes histologically proven presence of muscle-invasive bladder cancer (MIBC), clinical evidence of nodal or metastatic disease (as assessed by RECIST 1.1 criteria), radical cystectomy (RC), or death due to any cause. |
Secondary Outcome Measures
Measure: | Metastasis-free survival (MFS) |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | MFS is measured from time from randomization to first radiologic (as assessed by RECIST 1.1 criteria) or histologic evidence of metastatic disease or death due to any cause. |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | OS is defined as time from randomization to death. |
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | ORR is defined as proportion of participants who have complete response (CR) (defined as Negative biopsy, and Computed tomography/Magnetic resonance imaging [CT/MRI] of chest, abdomen, and pelvis showing no evidence of local recurrence, progression, or metastatic disease) or partial response (PR): (defined as down staging: biopsy proven non-muscle invasive disease less than [<] T1 and CT/MRI of chest, abdomen, and pelvis showing no evidence of metastatic disease) or non-response (those not achieving a complete response or down-staging, or those who do not undergo a biopsy will be considered non-responders). |
Measure: | Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE) |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | Number of Participants with AEs by Severity as assessed by CTCAE version 5 will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE. |
Measure: | Number of Participants with AEs by Severity according to Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | NCI PRO-CTCAE is a patient-reported outcome measure used to evaluate symptomatic toxicity in participants on cancer clinical trials. The NCI PRO-CTCAE is an item bank. The items selected for this study include all NCI PRO-CTCAE gastrointestinal items and urinary items. These items include taste changes, decreased appetite, nausea, vomiting, heartburn, gas, bloating, hiccups, constipation, diarrhea, abdominal pain, fecal incontinence, painful, urination, urinary urgency, urinary frequency, change in usual urine color, and urinary incontinence. |
Measure: | Number of Participants with Clinical Laboratory Abnormalities |
Time Frame: | Up to 8 years |
Safety Issue: | |
Description: | Number of participants with clinical laboratory abnormalities will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 31, 2021